关键词: BCAP31 NDC1 PI3K/AKT signaling hepatocellular carcinoma

Mesh : Animals Humans Mice Carcinogenesis Carcinoma, Hepatocellular / metabolism Cell Line, Tumor Cell Nucleus Division Cell Proliferation Cell Transformation, Neoplastic Liver Neoplasms / metabolism Membrane Proteins Phosphatidylinositol 3-Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism

来  源:   DOI:10.1002/jbt.23647

Abstract:
Hepatocellular carcinoma (HCC) is among the world\'s worst malignancies. Nuclear division cycle 1 (NDC1) is an essential membrane-integral nucleoporin, found in this study to be significantly increased in primary HCC. A multivariate analysis revealed that higher NDC1 expression was linked to worse outcome in HCC patients. Mouse xenograft tumors overexpressing NDC1 grew rapidly, and HCC cells overexpressing NDC1 showed enhanced proliferation, invasion, and migration in vitro. In contrast, knocking down NDC1 had the opposite effects in vitro. Furthermore, co-immunoprecipitation and liquid chromatograph mass spectrometer analyses revealed that NDC1 activated PI3K/AKT signaling by interacting with BCAP31. In summary, NDC1 and BCAP31 cooperate to promote the PI3K/AKT pathway, which is essential for HCC carcinogenesis. This suggests that NDC1 is predictive of prognosis in HCC.
摘要:
肝细胞癌(HCC)是世界上最严重的恶性肿瘤之一。核分裂循环1(NDC1)是一种重要的膜整合核孔蛋白,在这项研究中发现在原发性肝癌中显著增加。多变量分析显示,较高的NDC1表达与HCC患者预后较差有关。过表达NDC1的小鼠异种移植肿瘤生长迅速,和肝癌细胞过度表达NDC1显示增强的增殖,入侵,和体外迁移。相比之下,敲除NDC1在体外有相反的作用。此外,免疫共沉淀和液相色谱质谱仪分析显示NDC1通过与BCAP31相互作用激活PI3K/AKT信号传导。总之,NDC1和BCAP31协同促进PI3K/AKT通路,这对肝癌的发生至关重要。这表明NDC1可预测HCC的预后。
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